2017 Grants - Kastanenka

2017 Alzheimer's Association Research Grant (AARG)

How might the disruption of brain activity during sleep affect the progression of Alzheimer's disease?

Background
Background
During Alzheimer's disease, toxic brain changes disrupt the function of neurons (or nerve cells) in many ways. One neuronal function affected by Alzheimer's is called slow oscillation activity. Slow oscillations help form and consolidate memories during sleep, and they require the activity of several types of neurons. Scientists do not yet know which of these slow-oscillation-related neurons are disrupted in Alzheimer's disease. However, recent studies suggest that interneurons may be involved. Interneurons help transmit chemical messages among other groups of neurons, and the loss interneuronal function can severely affect slow oscillation and other activities linked to memory.

Research Plan
Ksenia Kastanenka, Ph.D., and her team will examine how Alzheimer's brain changes prevent interneurons from maintaining slow oscillation activity. Their effort will employ mice genetically engineered to develop human beta-amyloid, a protein fragment known to damage brain cells in Alzheimer's disease. The researchers will assess the effects of beta-amyloid exposure on two types of interneurons: "excitatory neurons" that promote cellular activity and "inhibitory neurons" that moderate this activity. Specifically, they will visualize and measure changes in the cells' calcium content — an indicator that the cells' activity levels have been disrupted.

Dr. Kastanenka's team will then evaluate two methods of restoring interneuronal function and slow oscillation activity in their mice. The first technique, called optogenetics, involves precisely controlled pulses of light that can activate the rodents' interneurons. The second method involves chemical compounds designed to strengthen interneuronal signaling. One or both of these methods may help moderate the progression of dementia in the rats.

Impact
If successful, this effort could shed new light on how slow oscillation activity and other brain cell network functions are affected by Alzheimer's disease. They could also lead to novel therapies that target these functions and possibly prevent Alzheimer's.